AB0306 IMPACT OF TOFACITINIB ON LIPID METABOLISM IN PATIENTS WITH RHEUMATOID ARTHRITIS: A REAL-WORLD STUDY
Authors: H. Huang, Y. Geng, Y. Fan, Z. Zhang
Journal: Annals of the Rheumatic Diseases (2023)

<h3>Background</h3> Tofacitinib is the first Janus Kinase (JAK) inhibitor available in China, and it has significantly improved the efficacy of treatment of rheumatoid arthritis (RA). Previous clinical trials found that tofacitinib can affect lipid metabolism in patients. <h3>Objectives</h3> Whether lipid and lipoprotein concentrations can recover by themselves and whether lipid-lowering drugs intervention is required, are currently inconclusive, and there is a lack of real-world experience. <h3>Methods</h3> Patients from the CENTRA (Collaboratively intENsive Treat-to-target in RA) cohort, a prospective follow-up cohort for RA in the Department of Rheumatology and Clinical Immunology, Peking University First Hospital were enrolled, and those who used lipid-lowering drugs were excluded. Patients were divided into tofacitinib exposure group and non-exposure group according to whether patients were prescribed with or without tofacitinib. Disease activity scores, TG, TCHO, HDL and LDL at baseline and during follow-up were calculated, and the ratios of TCHO/HDL to HDL/LDL was also calculated. Changes in lipid and lipoprotein concentrations after use of tofacitinib during follow-up were analyzed. Age, gender, disease duration, and the Simplified Disease Activity Index (SDAI) at baseline as covariates for propensity score matching was performed on patients with and without tofacitinib, and the lipid and lipoprotein profiles of the two groups were compared. <h3>Results</h3> A total of 304 patients were included, with 88 prescribed with tofacitinib and 216 without tofacitinib. (1) In patients with tofacitinib, the median TG and TCHO were 0.95 mmol/L and 4.45 mmol/L, respectively, the mean HDL and LDL were 1.32 mmol/L and 2.63 mmol/L at baseline, and the median TCHO/HDL and HDL/LDL ratios were 3.62 and 2.24, respectively. After 4 weeks of use of tofacitinib, the levels of TCHO, HDL and LDL increased compared with baseline by 16.6%, 12.9% and 14.4%, respectively. At week 12, LDL increased by 12.9% compared with baseline, indicating the returning to baseline levels, while the levels of TCHO and HDL were still significantly elevated. At week 48, TCHO also returned to baseline levels (increased by 2.9%). HDL levels remained elevated during follow-up. There were no significant increases in TG, TCHO/HDL and LDL/HDL ratios throughout the follow-up. In addition, there was no significant difference in lipid and lipoprotein changes between tofacitinib monotherapy (43 patients) and tofacitinib combined with csDMARDs (45 patients) during follow-up. (2) After 1:1 matched by propensity score matching, there were 83 patients prescribed with tofacitinib exposure and 83 without. In the 4 weeks of follow-up, there was no significant difference in the increase of lipid and lipoprotein between the two groups. At week 12, week 24, and week 48, the increase of TCHO in patients with tofacitinib was significantly higher than those without (0.47 vs. -0.1, p&lt;0.001; 0.33 vs.-0.06, p=0.001; 0.22 vs.-0.1, p=0.017). The LDL elevation in patient with tofacitinib was higher than that in patients without at week 12 and continued to week 24 (0.17 vs.-0.07, p=0.002; 0.18 vs.-0.09, p=0.001), but at week 48, there was no significant difference between the two groups compared with baseline. At week 12, patients in the tofacitinib-exposure group had higher HDL elevations (0.22 vs. 0.02, p &lt; 0.001), but there was no significant difference between the two groups form week 24 to week 48. Elevation in TG, THCO/HDL or LDL/HDL was not significantly different between the two groups throughout the follow-up. <h3>Conclusion</h3> After 4 weeks of using tofacitinib, TCHO, HDL and LDL levels increased in RA patients. LDL and TCHO returned to the baseline level at the week 12 and week 48, respectively, while HDL continued to increase. There was no significant change in TG, THCO/HDL or LDL/HDL throughout the follow-up. The elevation in lipid and lipoprotein profiles in RA patients prescribed with tofacitinib was significantly higher than those without. <h3>REFERENCES:</h3> NIL. <h3>Acknowledgements:</h3> NIL. <h3>Disclosure of Interests</h3> None Declared.